This invention concerns some new aminoethylphosphinic acid derivatives. Specifically the invention concerns some new aminoethylphosphinic acid derivatives which have antibacterial action.
Among the many antibacterial agents reported to date, compounds which inhibit the biosynthesis of cell wall peptidoglycan (not found in higher animals) are noted for their safety and their selective toxicity. They include the .beta.-lactams such as the penicillins, cephalosporins, single lactams and carbapenems, cycloserine, and bacitracin.
In the biosynthesis of cell wall peptidoglycan, the precursor which is UDP-MurNAc-Ala-D-Glu-Lys-D-Ala-D-Ala is first formed. Many enzymatic reactions are involved, including the conversion of L-Ala into D-Ala by the action of racemase, formation of D-Ala-D-Ala from D-Ala by the action of D-Ala-D-Ala ligase, and the binding of D-Ala D-Ala to UDP-MurNAc-Ala-D-Glu-Lys.
It is known that certain phosphonic acids have antibacterial action, as exemplified by alaphosphalin: ##STR1##
This compound is an inhibitor of bacterial cell wall synthesis. Its mechanism is reported to consist in the compound being taken up by the bacterium via the di-peptide transport system followed by scission of the peptide bond by the bacterium's peptidase, the 1-aminoethylphosphonic acid formed thereby inhibiting racemase activity.
(For examples, see Neuhaus, F.C. and Hammes, W.P.: Pharmacology & Therapeutics 14, 265-319, 1981; Atherton et al: Antimicrobial Agent and Chemotherapy 24, 552-528, 1983).
With this background, we sought a new and more effective antibacterial agent, and discovered the new type of aminoethylphosphonic acid derivatives to be described were effective agents. This discovery led to the present invention.